Fatty acid amido-methionine products

ABSTRACT

WHEREIN R is an aliphatic hydrocarbon chain of five to 29 carbon atoms. These compounds are especially useful in therapeutic and cosmetic preparations to be applied to human phaners, i.e. finger nails and hair.   Water-insoluble, lipo-soluble compounds consisting of fatty acid amido-methionines of the formula:

United States Patent Jean V. Morelle 170 Avenue Parmentier, 75 Paris, 10 ime,

[72] Inventor France [2|] Appl. No. 886,384 [22] Filed Dec. 18, 1969 [45] Patented Nov.30, 1971 [32] Priorities Oct. 13, 1966 France 79767;

May 31, 1967, France, No. 108515; Dec. 20, 1968, France, No. 179384 Continuation-impart of application Ser. No. 672,975, Oct. 5, 1967, now abandoned. This application Dec. 18, 1969, Ser. No. 886,384

[54] FATTY ACID AM1DOMETH1ON1NE PRODUCTS 4 Claims, No Drawings [52] U.S.CI 260/402.5, 424/319 [51 Int. Cl [50] Field of Searc Primary Examiner-Elbert L. Roberts AtlorneyArnold Robinson ABSTRACT: Water-insoluble, lipo-soluble compounds consisting offatty acid amido-methionines ofthe formula:

FATTY ACID AMlDO-METHIONINE PRODUCTS wherein R is an aliphatic hydrocarbon chain of five to 29 carbon atoms, thereby making RCO the acyl grouping from a fatty acid of six to 30 carbon atoms.

It has been known in the past that aminoacids could be acylated but that acylation has always resulted in surface active agents or detergents, generally in the form of highly detergent water-soluble, sodium slats, which were unsuitable for the purpose of the present invention.

in accordance with the present invention, there are provided compounds consisting of fatty acid amido-methionines of the formula:

wherein R is an aliphatic hydrocarbon chain of five to 29 carbon atoms.

The compounds of this invention are prepared by acylating methionine with a fatty acid or a fatty acid halide to produce a fatty acid amide-methionine salt. The obtained salt is treated with a strong acid or a cationic ion exchange resin to obtain the corresponding fatty acid amido-methionine.

The products of the present invention are particularly suitable for use in fields of therapeutics and cosmetics since they are lipo-soluble and their structure is similar to the structures of human phaners. These properties provide the products with the capability of penetrating easily through the tissues of 5 finger nails, toe nails, hair, etc., and they are accordingly useful in promoting regeneration of such tissues by providing the most important aminoacid which is needed for this purpose, i.e., methionine.

Methionine is one of the most important of the aminoacids for at least two reasons. Firstly, it contains sulfur which is essential in the protidic structures of the phaners; secondly, it is more important than cystine and cysteinewhich also contain sulfur-for, in the case of a deficiency in one of these aminoacids, methionine is able to convert into cystine and/or cysteine to reduce the deficiency. Proof of this conversion has been established by an experimentation using tagged sulfur in methionine.

Methionine in the form of fatty acid amido-methionines is especially interesting for this kind of structure. It is biosynthesized in an organism by the action of acylcoenzyme A whereas the corresponding methionine is freed from this structure by the action of SH-coenzyme A.

The products of the present invention are preferably prepared in a two-step process as described above.

The acylation is carried out by treatment of the methionine with a fatty acid or its functional equivalent, i.e. a fatty acid halide. The acids or the acid halides, the preferred halide being chloride, are those which contain six to 30 carbon atoms and may be saturated or unsaturated. Among these acids may be mentioned caproic, enanthic, caprylic, pelargonic, capric, undecanoic, lauric, tridecanoic, myristic, pentadecanoic, palmitic, margaric, stearic, nonadecanoic, eicosanoic, heneicosanoic, behenic, tricosanoic, lignocenic, pentacosanoic, cerotic, heptacosanoic, octacosanoic, nonacosanoic, triacontanoic, undecenoic, myristoleic, palmitoleic, oleic, erucic, and the like. it is intended, of course, the the naming of the foregoing acids includes the naming of their halides, such as chlorides, bromides, iodides, and fluorides, chlorides being the preferred halide. In general, the reaction takes place at ordinary temperatures, for example, 20-60 C. and the pH is maintained on the alkaline side, i.e. at about 7.5 to l l by the addition of a suitable material such as sodium hydroxide, sodium carbonate, ethyl chlorocarbonate, and the like. The reaction time varies with temperature but may require from about l5 minutes to several hours.

The acylation reaction may be considered to proceed generally as follows:

mN-o-ooon Elit O (CHDz-S-CH;

If the acylating agent is a free acid the byproduct of the equation is water and, if on the other hand, the acylating agent is an acid chloride, the byproduct is hydrogen chloride. in order to displace this reaction to the right, the byproduct water or hydrogen chloride should be removed as quickly as it is formed, which explains the reason for employing an alkaline material when hydrogen chloride is the byproduct. lf sodium hydroxide is employed as the alkaline agent it also tends to react with the acylating agent thus making it preferable to employ a slight stoichiometric excess of the acylating agent to provide enough for the principal reaction, for the reaction with the alkaline agent, and to force displacement of the reaction to the right.

The final step consists in treating the acylation product with a strong mineral acid such as hydrogen chloride or with an ion exchange resin. In one embodiment of this invention, the acylation product is acidified with hydrogen chloride and the compound of the invention accumulates as an upper layer, since it is insoluble in water, while the remaining material which is soluble remains in the aqueous layer.

In order to more fully understand the present invention, there is provided a detailed example in which a fatty acid amido-methionine is prepared. In general, the time, temperature, and other reaction conditions have been selected to give the best possible yield for each reaction. it is understood that modifications of these conditions can be made by those skilled in the art without deviating from the spirit of this invention. Parts and percentages are by weight and temperatures are in degrees centigrade unless otherwise specified.

EXAMPLE I First Step: Acylation a. By Acid Chloride Methionine is dissolved in water at the rate of about half a mole per liter and there is added sodium hydroxide and sodium carbonate to reach a pH of about lO-l l. Separately palmitic acid chloride mixed with acetone is prepared and then poured under agitation at room temperature in the methionine solution until stoichiometric proportions between methionine and palmitic chloride are obtained; pH values are controlled by the addition of sodium carbonate to prevent the pH from being lower than 8. After the end of the addition-the agitation is continued for 4 hours. The solution is ready for the second step.

b. By the Free Acid To an aqueous solution containing one part of methionine there is added concentration sodium hydroxide until a concentration of 2N is obtained and the solution is then chilled to a temperature between -5 and l C. A solution containin the stoichiometric amount of palmitic acid dissolved in ten times its volume of tetrahydrofuran is prepared, to which is added, by reference to the volume of the acid, 0.5 parts of ethyl chlorocarbonate and 0.7 parts of triethylamine. This solution of palmitic acid is then likewise cooled to a temperature between and 1 0 C. and slowly poured into the solution containing the methionine. The two solutions are mixed by agitation and the resulting mixture is cooled to prevent any rise in temperature during this step.

Other mixtures are possible for obtaining the compounds of the invention by using the free acid as starting material. It is possible to obtain the result while performing the reaction in the presence, for instance, of dicyclohexylcarbodiimide.

Second step: Recovery of Product The compound of the invention is recovered in the same manner whether the acylation agent is the acid chloride or the free acid. in either eventthe acylation product is acidified with an acid such as hydrogen chloride and the fatty acid amido-methionine which is insoluble in water accumulates as a layer on top of the aqueous layer. After decanting the supernatant layer, it is washed with water several times and then with benzene or other solvent to remove the last portions of palmitic acid or its chloride which may be present. The washed material is then steamed in a vacuum at a temperature of 50 C. and the fatty acid amido-methionine, i.e., palmitoyl methionine is obtained. The product has a melting point of 82-84 C. Acylation yield 90 percent. Analytical values for nitrogen 3.6 percent (Theory 3.2 percent) and sulfur 8 percent (Theory 7.1 percent).

in general, these compounds may be dehydrated by a short heating at 100 C.

EXAMPLES 25 The procedure of example i was repeated except that difmain characteristics of the compounds obtained are listed below in table I.

EXAM PLES 6-7 Hair lotions 6. Alcohol at 50! (voL) 98% Caprylic methionine 2';

7. Alcohol at (vol.) 98% undecenoic methionine 2% EXAMPLES 8-9 Detergent compositions for hair 8. Sodium lauroylsarcosinate at 20% 30% Caprylic methionine 2% Water 68% 9. Laurie methionine l0; Water Triethanolamine, (enough to make pH 7) EXAMPLES 10-1 1 Compositions for nails l0. Alcohol at 80% (vol.) 98% Llrloleic methionine 2% 1 l. Stearin l0; Polyoxyethylenate cetylic alcohol 5% Palmitie methionine 4 Water 81% IOOK' What is claimed is: 1. A water insoluble, lipo-soluble fatty acid amido methionine of the formulawherein R is an aliphatic hydrocarbon chain of 5 to 29 carbon atoms.

2. The compound of claim 1 wherein R is selected from the group consisting of capryl, lauryl, undecenyl, and linoleyl.

3. The process of preparing a fatty acid amido methionine of claim 1 which comprises (a) reacting methionine with a fatty acid or its halide containing 6 to 30 carbon atoms per molecule to produce a fatty acid amido methionine salt, and (b) reacting said salt with a strong acid or a cationic ion exchange resin to produce the desired fatty acid amido TABLE I Percent Compounds Melting Acylation Nitrogen Sulfur Q point, yield, Example Acylating agent 0 percent Found Theory Found Theory 2 Caprylic acid or its chloride. 73-75 98 4. 9 5 ll 11. 5 3 Laurie acid or its chloride. 68-70 )2 3. 0 4. 2 9. 5 ll. 6 4.. Undecenoic acid or its chlorid 57-69 88 4. 4 3. 9 l0 8. 4 5 Linoleic acid or its chloride... 93 3. 2 3 7. 5 7

The present invention relates also to some compositions 7 methionine.

concerning the treatment of hair and nails and which comprise as an active ingredient therein, at least one of the fatty acid amido-methionines hereinabove described.

Some examples of such compositions are given below.

4. The process of claim 4 wherein said fatty acid or its halide is selected from the group consisting of caprylic acid, caproyl chloride, lauric acid, lauroyl chloride, undecenoic acid, undecenoyl chloride, linoleic acid, and linoleic acid chloride. 

2. The compound of claim 1 wherein R is selected from the group consisting of capryl, lauryl, undecenyl, and linoleyl.
 3. The process of preparing a fatty acid amido methionine of claim 1 which comprises (a) reacting methionine with a fatty acid or its halide containing six to 30 carbon atoms per molecule to produce a fatty acid amido methionine salt, and (b) reacting said salt with a strong acid or a cationic ion exchange resin to produce the desired fatty acid amido methionine.
 4. The process of claim 4 wherein said fatty acid or its halide is selected from the group consisting of caprylic acid, caproyl chloride, lauric acid, lauroyl chloride, undecenoic acid, undecenoyl chloride, linoleic acid, and linoleic acid chloride. 